title: Rational drug design based synthesis of novel arylquinolines as anti-tuberculosis agents.
abstract: A series of novel arylquinoline derivatives was designed retaining significant pharmacophoric features and three dimensional geometry of bedaquiline. In silico ADME study was performed to assess drug likeness and toxicity profiles of the designed molecules. The compounds were evaluated for activity against Mycobacterium tuberculosis H37Rv using Resazurin Microtitre Assay (REMA) plate method and cytotoxicity in VERO C1008 cell line. Several of the synthesized compounds exhibited good antituberculosis activity and selectivity, especially compounds, 12i (MIC: 5.18 μM and MIC/CC50: 152.86) and 12l (MIC: 5.59 μM and MIC/CC50: 160.57). The study opens up a new platform for the development of arylquinoline based drugs for treating tuberculosis.
authors.affiliation: Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
authors.forename: Puneet P
authors.initials: PP
authors.lastname: Jain
authors.forename: Mariam S
authors.initials: MS
authors.lastname: Degani
authors.forename: Archana
authors.initials: A
authors.lastname: Raju
authors.forename: Muktikanta
authors.initials: M
authors.lastname: Ray
authors.forename: M G R
authors.initials: MG
authors.lastname: Rajan
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002384:Catalysis; D002522:Chlorocebus aethiops; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011487:Protein Conformation; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D011804:Quinolines; D000251:Adenosine Triphosphatases
keywords: ATP synthase; Arylquinoline; Bedaquiline; Mycobacterium tuberculosis